Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high-fat diet

FASEB J. 2015 Jul;29(7):2690-701. doi: 10.1096/fj.14-268979. Epub 2015 Mar 2.


Alcohol consumption throughout pregnancy can cause metabolic dysregulation, including glucose intolerance in progeny. This study determined if periconceptional (PC) alcohol (12% v/v in a liquid diet) (PC:EtOH) consumed exclusively around conception results in similar outcomes in Sprague-Dawley rats. Control (C) rats were given a liquid diet containing no alcohol but matched to ensure equal caloric intake. PC maternal alcohol intake (from 4 days before conception until day 4 of gestation), resulted in offspring with elevated fasting plasma glucose (∼10-25%, P < 0.05), impaired glucose tolerance (P < 0.05), and decreased insulin sensitivity (P < 0.01) at 6 months of age. This was associated with increased hepatic gluconeogenesis and sex-specific alterations in peripheral protein kinase B (AKT) signaling. These changes were accompanied by increased mRNA expression of DNA methyltransferases (DNMTs) 1, 3a, and 3b (1.5- to 1.9-fold, P < 0.05) in fetal liver in late gestation, suggesting PC:EtOH may cause epigenetic changes that predispose offspring to metabolic dysfunction. Exposure to a postnatal (PN) high-fat and cholesterol diet (HFD) from 3 months of age caused hyperinsulinemia (∼2-fold increase, P < 0.001) and exacerbated the metabolic dysfunction in male offspring exposed to PC:EtOH but had no additive effects in females. Given many women may drink alcohol while planning a pregnancy, it is crucial to increase public awareness regarding the effects of alcohol consumption around conception on offspring health.

Keywords: developmental programming; diabetes; gene expression; gluconeogenesis; metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Animals
  • Blood Glucose / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • Diet, High-Fat / adverse effects
  • Female
  • Fertilization
  • Fetus / metabolism
  • Gluconeogenesis
  • Glucose Intolerance / etiology*
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Histone Deacetylases / genetics
  • Humans
  • Insulin Resistance*
  • Liver / metabolism
  • Male
  • Models, Animal
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Signal Transduction


  • Blood Glucose
  • RNA, Messenger
  • DNA (Cytosine-5-)-Methyltransferases
  • Histone Deacetylases